# Mechanisms of Pancreatic Fibrosis

> **NIH NIH R01** · DUKE UNIVERSITY · 2024 · $347,760

## Abstract

Abstract
Repeated or prolonged injury to the pancreas leads to loss of normal exocrine and endocrine tissue and
pancreatic fibrosis. Fibrosis of the pancreas which can lead to stricturing of the common bile and pancreatic
ducts with resultant duct obstruction. Importantly, pancreatic duct obstruction may contribute to the
development of chronic pancreatitis even in the absence of other pancreatic injury. For example, increased
pancreatic duct pressure itself can cause chronic pancreatitis and pancreatic fibrosis. Therefore, it appears
that the pancreas can sense pressure and pressure causes pancreatic injury.
Pancreatic fibrosis results from the deposition of extracellular matrix by activated pancreatic stellate cells
(PSCs). Under normal conditions PSCs reside in the pancreas in a quiescent state but are converted to an
active state when the pancreas is injured. Activated PSCs secrete collagen and other proteins to cause
fibrosis. The observation that pancreatic duct obstruction and pressure, itself, can induce pancreatic fibrosis
even in the absence of inflammation, led us to ask if PSCs can sense pressure? And if so, how?
The recent discovery that pressure sensitivity could be conveyed through cell surface, mechanically-activated
ion channels led us to examine these proteins in the pancreas. We recently discovered that the mechanically-
activated ion channel Piezo1 is highly expressed in PSCs. Our preliminary data indicate that pressure
sensitivity in the pancreas is conveyed by Piezo1 and that Piezo1 activation may be linked to PSC activation.
Therefore, we hypothesize that pressure within the pancreas causes pancreatic fibrosis by stimulating
Piezo1 in pancreatic stellate cells (PSCs). In the current proposal, we will determine if this pathway is the
mechanism linking pancreatic duct obstruction with pancreatic fibrosis. We believe these studies will identify a
novel mechanism for the development of pancreatic fibrosis. Moreover, we will determine if blocking
mechanically activated ion channels and their signaling pathways protect against pancreatic fibrosis. Overall,
this project will yield novel insights into the initiation of pancreatic fibrosis and could unveil a novel target for
preventing its complications.

## Key facts

- **NIH application ID:** 10843772
- **Project number:** 5R01DK124474-05
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Rodger A. Liddle
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $347,760
- **Award type:** 5
- **Project period:** 2020-09-18 → 2026-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10843772

## Citation

> US National Institutes of Health, RePORTER application 10843772, Mechanisms of Pancreatic Fibrosis (5R01DK124474-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10843772. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*